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HLA compatibility is considered the key criterion for selecting donors for allo-HSCT. DKMS study data presented at the DGHO Annual Meeting 2025 in Cologne indicate the biological age of donors has a greater influence on transplant success than previously assumed [1]. “Our results show that we need to reevaluate the established standard for donor selection,” says Prof. Dr. Johannes Schetelig, Head of Stem Cell Transplantation Unit at the University Hospital Carl Gustav Carus Dresden and Director Clinical Research at DKMS. The international non-profit supports people with blood cancer and promotes research. Its campaigns encourage young people aged 17+ to register as stem cell donors.
The selection of suitable donors is crucial for the long-term recovery of patients after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Primarily, the transplantation from a matched sibling donor (MSD) is considered the “first choice” [2]. It is associated with a low risk of non-relapse mortality (NRM) and rejection reactions such as acute graft-versus-host disease (GvHD) [3].
Thanks to improved matching strategies, optimized pre-treatments, and newer options for GvHD prophylaxis, matched unrelated donors (MUDs) or mismatched unrelated donors (MMUDs), with minor differences in human leukocyte antigens (HLA), can also be considered. Stem cell transplantations from haploidentical family donors whose HLA characteristics only partially match are also possible [2]. In addition to HLA characteristics, additional donor attributes are gaining importance in donor selection. More than five years ago, a study based on more than 10,000 patients and their HLA-compatible, unrelated stem cell donors investigated the influence of biological gender, age, and blood type. The study showed that only the age of the donor was significantly associated with survival. The study found that the 2-year survival rate decreased by around three percent for every ten years of donor age [4]. Further studies followed with the aim of creating a reliable, data-based decision-making basis for selecting optimal stem cell donors.
Young age alongside HLA matching is a decisive factor for success
The latest retrospective registry study published by Prof. Schetelig et al. in October 2025 in the journal Leukemia now confirms that the age of the donor plays a major role in the success of transplantation, even more so than previously assumed [1]. The results showed that patients over the age of 50 with myeloid cancers have better survival chances with allogeneic stem cell transplantation if the stem cells come from young, HLA-compatible, unrelated donors than from older, HLA-identical siblings. “Further studies need to be conducted to understand the underlying biology and differences in immune reconstitution,” said Schetelig. The findings could influence clinical practice, where MSD is currently often preferred over MUD regardless of age.
The study examined 3,460 patients aged 50 and older with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), and MDS/MPN who had received their first allogeneic HSCT. Patients received either a donation from an MSD (1,235) aged 50 years or older or a MUD aged between 18 and 35 years (2,225). After multivariable adjustment, the MUD group showed a significant risk reduction compared to the MSD group [1]:
• 14% in event-free survival (EFS), p = 0.003
• 18% in overall survival (OS), p < 0.001
• 16% in relapse risk, p = 0.018
The greater the age difference between two donors, the greater the impact on survival.
Gender and CMV status also play a role
In addition to age, the study by Schetelig et al. [1] also examined gender and cytomegalovirus (CMV) status. An advantageous constellation was defined as one in which the CMV serostatus of the donor and patient matched and no female donor donated to a male patient. The results showed that in favorable combinations, the EFS and OS of patients with HLA-compatible young unrelated donors was significantly better than with older sibling donors. When young unrelated donors had an unfavorable constellation, the survival chances for patients were as good as with older sibling donors [1]. “This means that unrelated donors can be selected without any disadvantages,” Schetelig concluded.
New findings from the HAMLET study: haploidentical versus mismatched
The as-yet-unpublished HAMLET study (HAploidentical versus Mismatched UnreLatEd Donor Transplantation) by DKMS, the results of which Prof. Schetelig presented once again at the poster session of the Annual Meeting of the German, Austrian and Swiss Societies for Hematology and Medical Oncology (DGHO), addressed the question of which factors are decisive for the selection of donors. The study found no relevant difference between haploidentical family donors and unrelated donors with a mismatch (MMUD, 9/10 mismatch) [5]. The prospective study focused on patients with AML/MDS and acute lymphoblastic leukemia (ALL) who had neither HLA-identical sibling donors nor HLA-compatible unrelated donors. The study data also showed an age effect for non-fully compatible donors: patients with younger donors had a better 2-year survival rate. “The influence of other HLA and non-HLA factors needs to be further investigated to enable the selection of the best donor for a transplant recipient,” Schetelig emphasizes.
Despite numerous studies on the subject, Schetelig believes that these are insufficient to adequately reflect the selection decision in practice. “In everyday clinical practice, the main focus is on the urgency of the transplant and the availability of donors. Against this background, the degree of kinship can still be a major factor.” The aim of current research is also to better understand why stem cells from young donors are advantageous. Is it the fitness of the stem cells or the transfer of the young immune system? The fact is: “When donating stem cells, a young donor age can be crucial,” emphasizes Schetelig. “Young people can save lives by registering as stem cell donors.”
Further information on registration can be found on the DKMS website https://www.dkms.org/.
References:
1. Schetelig J, et al. Leukemia 2025; 39(10):2523–2532. doi: 10.1038/s41375-025-02724-1
2. German Onkopedia Guideline „Spenderauswahl“, as of January 2021, available at: https://www.onkopedia.com/de/onkopedia/guidelines/spenderauswahl/@@guideline/htm...
3. Salvatore D, et al. Haematologica 2018; 103(8):1317–1328. doi: 10.3324/haematol.2018.189258
4. Shaw BE, et al. Biol Blood Marrow Transplant 2018;24(5):1049–1056. doi: 10.1016/j.bbmt.2018.02.006
5. Stölzel F, et al., präsentiert auf dem DGHO 2025, Köln 24-27.Oktober, P492.
About HAMLET study
98 adult patients with high-risk AML, ALL, or MDS were randomized 1:1 and received a haploidentical family donation and 50 mg/kg PTCy on days +3 and +4 or a donation from mismatched unrelated donors (MMUD – single mismatch in HLA-A, -B, -C, or -DRB1) and 10 mg/kg ATG on days -1 to -3. The study was terminated after 98 patients were enrolled between February 2018 and April 2023 due to slow recruitment. The primary endpoint was overall survival (OS). For the analysis of the primary endpoint, a hazard ratio (HR) of 0.85 for MMUD versus haploidentical family donations was set as the non-inferiority limit, and we tested at a one-sided significance level of 5% [5].
About DKMS
DKMS is an international non-profit organization dedicated to saving the lives of patients with blood cancer and blood disorders. Founded in Germany in 1991 by Dr Peter Harf, DKMS and the organization’s over 1,500 employees have since relentlessly pursued the aim of giving as many patients as possible a second chance at life. With over 13 million registered donors, DKMS has succeeded in doing this more than 130,000 times to date by providing blood stem cell donations to those in need. This accomplishment has led to DKMS becoming the global leader in the facilitation of unrelated blood stem cell transplants. The organization has offices in Germany, the US, Poland, the UK, Chile, India and South Africa. International expansion and collaboration are key to helping patients worldwide because, like the organization itself, blood cancer knows no borders.
DKMS is also heavily involved in the fields of medicine and science, with its own research unit focused on continually improving the survival and recovery rate of patients. In its high-performance laboratory, the DKMS Life Science Lab, the organization sets worldwide standards in the typing of potential blood stem cell donors. With its international support programs, the organization improves the access to treatment for patients in low and middle-income countries.
Schetelig J., et al: Young unrelated donors confer a survival advantage for patients with myeloid malignancies compared to older siblings. Leukemia 2025; 39(10):2523–2532.
https://www.nature.com/articles/s41375-025-02724-1
https://professional.dkms.org/ Find more information about DKMS's commitment to medicine and research.
https://www.dkms.org/ Further information on registration can be found on the DKMS website.
Recent studies show that donor age – in addition to genetic factors – is an important determinant of ...
Quelle: Uwe Weiser
Copyright: © DKMS
Prof. Dr. Johannes Schetelig, Director Clinical Research at DKMS and Head of the Stem Cell Transplan ...
Copyright: © DKMS
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